Microchip and particulate analyzing device

ABSTRACT

A microchip is provided, which includes a substrate including a fluid channel structure. The fluid channel structure includes a first fluid introduction channel and a second fluid introduction channel configured to meet so as to allow merging of a first fluid introduced from the first fluid introduction channel and a second fluid introduced from the second fluid introduction channel. A tapered portion is configured to be positioned after merging the first fluid and the second fluid so as to suppress a spiral flow field generated after the merging.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. application Ser. No.16/927,305, filed on Jul. 13, 2020, which is a continuation of U.S.application Ser. No. 14/879,639, filed on Oct. 9, 2015, which is acontinuation of U.S. application Ser. No. 13/580,912, filed on Aug. 23,2012, which is a national stage of International Application No.PCT/JP2011/000902 filed on Feb. 18, 2011, which claims priority toJapanese Patent Application No. 2010-043968 filed on Mar. 1, 2010, thedisclosures of each of which are incorporated herein by reference.

TECHNICAL FIELD

The present invention relates to a microchip and a particulate analyzingdevice. More particularly, the present invention relates to a microchipor the like for optically, electrically or magnetically analyzing thecharacteristics of particulates such as cells or microbeads in channels.

BACKGROUND

In recent years, microchips have been developed in which an area and/ora channel or channels for performing chemical and biological analysesare provided by application of micro-machining techniques used in thesemiconductor industry. These microchips have begun to be utilized forelectrochemical detectors in liquid chromatography, smallelectrochemical sensors in medical service sites, and the like.

Analytical systems using such microchips are called micro-TAS(micro-Total-Analysis System), lab-on-a-chip, bio chip or the like, andis paid attention to as a technology by which chemical and biologicalanalyses can be enhanced in speed, efficiency and level of integrationor by which analyzing devices can be reduced in size.

The micro-TAS, which enables analysis with a small amount of sample andenables disposable use of microchips, is expected to be appliedparticularly to biological analyses where precious trace amounts ofsamples or a multiplicity of specimens are treated.

An application example of the micro-TAS is a particulate analyzingtechnology in which characteristics of particulates such as cells andmicrobeads are analyzed optically, electrically or magnetically inchannels arranged on microchips. In the particulate analyzingtechnology, fractional collection of a population satisfying apredetermined condition or conditions from among particulates on thebasis of analytical results of the particulates is also conducted.

Patent Literature 1, Japanese Patent Laid-open No. 2003-107099, forexample, discloses “a particulate fractionation microchip having achannel for introducing particulate-containing solution, and a sheathflow forming channel arranged on at least one lateral side of theintroducing channel.” The particulate fractionation microchip furtherhas “a particulate measuring section for measuring the particulatesintroduced, at least two particulate fractionating channels disposed onthe downstream side of the particulate measuring section so as toperform fractional collection of the particulates, and at least twoelectrodes disposed in the vicinity of channel ports opening from theparticulate measuring section into the particulate fractionatingchannels so as to control the moving direction of the particulates.”

The particulate fractionation microchip disclosed in Patent Literature1, typically, is so designed that fluid laminar flows are formed by a“trifurcated channel” having a channel for introducing aparticulate-containing solution and two sheath flow forming channels(see “FIG. 1” of the literature).

FIGS. 17A and 17B show a trifurcated channel structure according torelated art (FIG. 17A), and sample liquid laminar flows formed by thechannel structure (FIG. 17B). In the trifurcated channel, a sampleliquid laminar flow passing through a channel 101 in the direction ofsolid-line arrow in FIG. 17A can be sandwiched, from the left and rightsides, by sheath liquid laminar flows introduced through channels 102,102 in the directions of dotted-line arrows in the figure. By this, asshown in FIG. 17B, the sample liquid laminar flow can be fed through thecenter of the channel. Incidentally, in FIG. 17B, the sample liquidlaminar flow is depicted in solid lines, and the channel structure indotted lines.

According to the trifurcated channel shown in FIGS. 17A and 17B, thesample liquid laminar flow is sandwiched by the sheath liquid laminarflows from the left and right sides, whereby with respect to thesandwiching direction (the Y-axis direction in FIGS. 17A and 17B), thesample liquid laminar flow can be fed in the state of being deflected toan arbitrary position in the channel. With respect to the verticaldirection (the Z-axis direction in FIGS. 17A and 17B) of the channel,however, it has been very difficult to control the sample liquid feedingposition. In other words, in the trifurcated channel according torelated art, it has only been possible to form the sample laminar flowthat is oblong in the Z-axis direction.

Therefore, the microchip having the trifurcated channel according torelated art has the problem that in the case where, for example, aparticulate-containing solution as a sample liquid is made to flowthrough a channel and subjected to optical analysis, there would be adispersion of the feeding position of the particulates in the verticaldirection (depth direction) of the channel. Therefore, there has beenthe problem that the flowing speed of particulates differs depending onthe feeding position of the particulates, variation of detection signalsincreases, and the accuracy of analysis is degraded.

Patent Literature 2, Japanese Examined Patent Publication No. 7-119686,discloses a channel structure that introduces a sample liquid into thecenter of a sheath liquid laminar flow from an opening at the center ofthe channel through which the sheath liquid laminar flow is fed tothereby feed the sample liquid laminar flow being surrounded by thesheath liquid laminar flow (see FIGS. 2 and 3 of the literature). Thechannel structure enables the sample liquid to be introduced into thecenter of the sheath liquid laminar flow, thereby eliminating thedispersion of the feeding position of the particulates in the depthdirection of the channel, so that the high accuracy of analysis can beobtained.

FIGS. 18A and 18B show a channel structure according to related artapplied for introducing a sample liquid to the center of a sheath liquidlaminar flow (FIG. 18A), and a sample liquid laminar flow formed by thechannel structure (FIG. 18B). In this channel structure, the sheathliquid laminar flow is introduced into each of channels 102 and 102 inthe direction of arrow T in FIG. 18A and fed to a channel 103. Then, thesample liquid fed to a channel 101 in the direction of arrow S can beintroduced from an opening 104 to the center of the sheath liquidlaminar flow fed through the channel 103. The sample liquid laminar flowcan be thereby fed, being converged to the center of the channel 103, asshown in FIG. 18B. In FIG. 18B, the sample liquid laminar flow isdepicted in solid lines, and the channel structure in dotted lines.

On the other hand, in Patent Literature 2, it is pointed out that, whenintroducing the sample liquid laminar flow into the sheath liquidlaminar flow in such a channel structure, turbulence occurs in thesample liquid laminar flow, which raises the case where the sampleliquid laminar flow is not a flat and stable laminar flow (see the rows12 to 46 in the right column on page 4 of the literature). Note that“flat laminar flow” indicates a laminar flow converted in the depthdirection (the Z-axis direction) of the channel in FIGS. 18A and 18B,and “non-flat laminar flow” indicates a laminar flow dispersed andspread in the depth direction of the channel.

In the above Patent Literature, it is proposed to provide the opening ofthe channel through which the sample liquid laminar flow is introducedwith a pair of plate projections (see the reference numeral 18 in FIG.10 of the literature) or the like in order to suppress the turbulence(wake) of the laminar flow at the merging portion of the sample liquidlaminar flow and the sheath liquid laminar flows. The plate projections18 extend from the opening wall of the channel through which the sampleliquid laminar flow is introduced in the flowing direction of the sampleliquid laminar flow and guides the sample liquid flowing out from theopening.

SUMMARY

With the plate projections 18 disclosed in the above Patent Literature2, it is possible to guide the sample liquid flowing out from theopening and let the sample liquid flow through the channel as a stablelaminar flow converged in the depth direction of the channel.

However, the channel structure is complicated when such a guidestructure is provided at the opening of the channel through which thesample liquid laminar flow is introduced. Further, it is necessary tolaminate three or more substrate onto one another in order to form sucha channel structure on a microchip. Therefore, high accuracy is neededfor the formation of the channel structure on each substrate and thelamination of the substrates, which increases the manufacturing cost ofthe microchip.

In light of the foregoing, it is desirable to provide a microchipcapable of feeding a sample liquid laminar flow converged to the centerof a channel and easily manufacturable.

According to an embodiment of the present invention, there is provided amicrochip, which includes a substrate including a fluid channelstructure. The fluid channel structure includes a first fluidintroduction channel and a second fluid introduction channel configuredto meet so as to allow merging of a first fluid introduced from thefirst fluid introduction channel and a second fluid introduced from thesecond fluid introduction channel. A tapered portion is configured to bepositioned after merging the first fluid and the second fluid so as tosuppress a spiral flow field generated after the merging.

According to another embodiment of the present invention, there isprovided a particulate analyzing device, which includes a microchipincluding a substrate that includes a fluid channel structure. The fluidchannel structure includes a first fluid introduction channel and asecond fluid introduction channel configured to meet so as to allowmerging of a first fluid introduced from the first fluid introductionchannel and a second fluid introduced from the second fluid introductionchannel. A tapered portion is configured to be positioned after mergingthe first fluid and the second fluid so as to suppress a spiral flowfield generated after the merging.

According to yet another embodiment of the present invention, there isprovided a method of manufacturing a microchip. A substrate including afluid channel structure is provided. The fluid channel structureincludes a first fluid introduction channel and a second fluidintroduction channel configured to meet so as to allow merging of afirst fluid introduced from the first fluid channel and a second fluidintroduced from the second fluid introduction channel. A tapered portionis configured to be positioned after merging the first fluid and thesecond fluid from the first and second fluid introduction channels tosuppress a spiral flow field generated after the merging.

It should be noted that the “particulates” in the present embodimentwidely include microscopic bioparticles such as cells, microorganisms,liposome, etc. as well as synthetic particles such as latex particles,gel particles, industrial particles, etc. The microscopic bioparticlesinclude chromosome, liposome, mitocondria, organelle, etc. whichconstitute various cells. The cells here include animal cells (bloodcorpuscle cells, etc.) and plant cells. The microorganisms includesbacteria such as colibacillus, etc., viruses such as tobacco mosaicvirus, etc., and fungi such as yeast, etc. Further, the microscopicbioparticles may include also microscopic biopolymers such as nucleicacid, proteins, and complexes thereof. The industrial particles may be,for example, organic or inorganic polymer materials, metals or the like.The organic polymer materials include polystyrene, stylene-vinylbenzene,and polymethyl methacrylate. The inorganic polymer materials includeglass, silica, and magnetic materials. The metals include gold colloidand aluminum. The shape of these particulates is usually spherical, butmay be non-spherical. Besides, the particulates are not particularlylimited as to size, mass or the like.

According to the embodiments of the present invention described above, amicrochip capable of feeding a sample liquid laminar flow converged tothe center of a channel and easy manufacturability is provided.

BRIEF DESCRIPTION OF DRAWINGS

FIGS. 1A and 1B are schematic diagrams illustrating a channel structureon a microchip according to a first embodiment of the present invention,in which FIG. 1A shows a top view and

FIG. 1B shows a sectional view;

FIGS. 2A, 2B and 2C are schematic diagrams illustrating sections of amerge channel 12 of the microchip according to the first embodiment ofthe present invention, in which FIG. 2A shows section P-P, FIG. 2B showssection Q-Q, and FIG. 2C shows section R-R, respectively in FIGS. 1A and1B;

FIG. 3 is a schematic diagram illustrating a structure of acommunicating port 111 of the microchip according to the firstembodiment of the present invention;

FIGS. 4A and 4B are schematic diagrams illustrating a structure of thecommunicating port 111 of the microchip according to the firstembodiment of the present invention (FIG. 4A) and an opening 104 of achannel structure according to related art shown in FIGS. 18A and 18B(FIG. 4B);

FIGS. 5A, 5B and 5C are schematic diagrams illustrating alternativeexamples of a tapered portion 122 of the microchip according to thefirst embodiment of the present invention, in which the upper part showsa top view and the lower part shows a sectional view;

FIGS. 6A and 6B are schematic diagrams illustrating a channel structureon a microchip according to a second embodiment of the presentinvention, in which FIG. 6A shows a top view and FIG. 6B shows asectional view;

FIGS. 7A, 7B and 7C are schematic diagrams illustrating sections of amerge channel 12 of the microchip according to the second embodiment ofthe present invention, in which FIG. 7A shows section P-P, FIG. 7B showssection Q-Q, and FIG. 7C shows section R-R, respectively in FIGS. 6A and6B;

FIGS. 8A, 8B, and 8C are schematic diagrams illustrating alternativeexamples of a tapered portion 123 of the microchip according to thesecond embodiment of the present invention, in which the upper partshows a top view and the lower part shows a sectional view;

FIGS. 9A and 9B are schematic diagrams illustrating taper angles in adepth direction of a channel of the tapered portion 123 of the microchipaccording to the second embodiment of the present invention, in whichthe upper part shows a top view and the lower part shows a sectionalview;

FIGS. 10A and 10B are schematic diagrams illustrating an alternativeexample of a tapered portion 123 and a contracted position 121 of themicrochip according to the second embodiment of the present invention,in which FIG. 10A shows a top view and FIG. 10B shows a sectional view;

FIGS. 11A and 11B are schematic diagrams illustrating a channelstructure on a microchip according to a third embodiment of the presentinvention, in which FIG. 11A shows a top view and FIG. 11B shows asectional view;

FIGS. 12A, 12B and 12C are schematic diagrams illustrating sections of amerge channel 12 of the microchip according to the third embodiment ofthe present invention, in which FIG. 12A shows section P-P, FIG. 12Bshows section Q-Q, and FIG. 12C shows section R-R, respectively in FIGS.11A and 11B;

FIG. 13 is a schematic diagram illustrating an alternative example oftapered portions 122 and 123 of the microchip according to the thirdembodiment of the present invention, in which the upper part shows a topview and the lower part shows a sectional view;

FIGS. 14A and 14B are schematic diagrams illustrating an alternativeexample of a tapered portion 123 and a contracted position 121 of themicrochip according to the third embodiment of the present invention, inwhich FIG. 14A shows a top view and FIG. 14B shows a sectional view;

FIGS. 15A and 15B are diagrams illustrating a manufacturing method of amicrochip according to an embodiment of the present invention, whichshow top schematic diagrams of substrates constituting a chip;

FIGS. 16A and 16B are schematic diagrams illustrating a manufacturingmethod of a microchip according to an embodiment of the presentinvention, in which FIG. 16B shows a section along P-P in FIG. 16A;

FIGS. 17A and 17B are schematic diagrams illustrating a trifurcatedchannel structure according to related art (FIG. 17A), and sample liquidlaminar flows formed by the channel structure (FIG. 17B);

FIGS. 18A and 18B are schematic diagrams illustrating a channelstructure according to related art applied for introducing a sampleliquid to the center of sheath liquid laminar flows (FIG. 18A), andsample liquid laminar flows formed by the channel structure (FIG. 18B).

FIGS. 19A and 19B are schematic diagrams illustrating the channelstructure according to related art shown in FIGS. 18A and 18B, in whichFIG. 19A shows a top view and FIG. 19B shows a sectional view;

FIGS. 20A, 20B and 20C are schematic diagrams illustrating a fluidvelocity vector field in the channel structure according to related artshown in FIGS. 18A and 18B, in which FIG. 20A shows section P-P, FIG.20B shows section Q-Q, and FIG. 20C shows section R-R, respectively inFIGS. 19A and 19B; and

FIG. 21 is a schematic diagram illustrating a fluid velocity vectorfield in the channel structure according to related art shown in FIGS.18A and 18B.

DETAILED DESCRIPTION

Preferred embodiments for carrying out the present invention will bedescribed hereinafter with reference to the drawings. Note that theembodiments described below are typical exemplary embodiments of thepresent invention, and the invention is not to be narrowly construed dueto the embodiments.

1. Fluid Velocity Vector Field in Channel Structure According to RelatedArt

The channel structure according to related art which is applied forintroducing a sample liquid to the center of a sheath liquid laminarflow, shown in FIGS. 18A and 18B, has the problem that, when introducingthe sample liquid laminar flow into the sheath liquid laminar flow,turbulence occurs in the sample liquid laminar flow, and the sampleliquid laminar flow is not converted to the center of the channel.

Specifically, referring to FIGS. 19A and 19B, in the case where a sampleliquid laminar flow S is introduced from an opening 104 to the center ofsheath liquid laminar flows T respectively introduced to channels 102and 102 and flowing through a channel 103, the sample liquid laminarflow S is dispersed in the depth direction of the channel (the Z-axisdirection) in some cases. If the sample liquid laminar flow S is notconverted to the center of the channel, the feeding position of theparticulates contained in the sample liquid laminar flow S is dispersedin the depth direction of the channel, and therefore, the detectionsignal of the particulates also varies, which causes degradation of theaccuracy of analysis.

The inventors of the present invention have conducted numericalcalculation of the fluid velocity vector field (flow field) in thechannel structure in order to find a factor of the turbulence of thesample liquid laminar flow occurring in the channel structure accordingto related art. As a result, they have found that the spiral flow fieldgenerated after the merging of the sample liquid laminar flow and thesheath liquid laminar flows causes the turbulence of the sample liquidlaminar flow.

The fluid velocity vector field in the channel structure according torelated art is described with reference to FIGS. 19A and 19B and FIGS.20A to 20C. FIGS. 20A to 20C are schematic sectional diagrams of thechannel structure according to related art, in which FIG. 20A showssection P-P, FIG. 20B shows section Q-Q, and FIG. 20C shows section R-R,respectively in FIGS. 19A and 19B.

When the sample liquid laminar flow S is introduced from the opening 104into the center of the sheath liquid laminar flow T fed through thechannel 103, a high velocity vector appears at the center in the depthdirection of the channel immediately after the introduction (see thearrows in FIG. 20A). It is considered that the high velocity vectoroccurs because the merged sample liquid laminar flow S and sheath liquidlaminar flows T are concentrated on the center of the depth direction ofthe channel for flowing faster.

Further, in the process that the flow fields from the channel 101 andthe channels 102 and 102 are merged into one flow field, a high velocityvector occurring at the center in the depth direction of the channelgrows into the flow field that rotates in the Z-axis positive ornegative direction as shown in FIG. 20B, and further grows into thespiral flow field as shown in FIG. 20C. Then, it has been founded thatthe sample liquid laminar flow S is stretched out in the Z-axis positiveand negative direction and dispersed in the depth direction of thechannel. It has been also found that the deformation of the sampleliquid laminar flow S due to the spiral flow field becomes moresignificant depending on the flow rate of the sheath liquids fed fromthe channels 102 and 102.

Furthermore, the inventors of the present invention have found, as aresult of the numerical calculation of the fluid velocity vector field(flow field), that a slow flow field occurring near the opening forintroducing the sample liquid laminar flow into the center of the sheathliquid laminar flow causes the turbulence of the sample liquid laminarflow.

FIG. 21 schematically illustrates a slow flow field occurring in thevicinity of an opening 104 of the channel structure according to relatedart, shown in FIGS. 18A and 18B, which is applied for introducing thesample liquid to the center of the sheath liquid laminar flow.

In the vicinity of the opening 104, a shear force occurs between thesheath liquid laminar flows T and the sample liquid laminar flow S dueto the merging of the sheath liquids fed from the channels 102 and 102and the sample liquid flowing out from the opening 104. It has beenfound that, by the shear force, a slow velocity vector occurs in thevicinity of the opening 104, and an unstable flow field with a stagnantflow is generated. Due to the stagnant flow field, the sample liquidlaminar flow S becomes unstable and dispersed in the depth direction ofthe channel. It has been also found that the deformation of the sampleliquid laminar flow S due to the stagnant flow field becomes moresignificant as the flow rate of the sample liquid flowing out of theopening 104 is lower.

2. Microchip According to First Embodiment of Invention

A first feature of a microchip according to an embodiment of the presentinvention is to provide a channel structure that suppresses theabove-described spiral flow field generated after merging of the sampleliquid laminar flow and the sheath liquid laminar flows and therebyavoids the turbulence of the sample liquid laminar flow. A secondfeature of a microchip according to an embodiment of the presentinvention is to provide a channel structure that suppresses theabove-described stagnant flow field generated in the vicinity of anopening for introducing the sample liquid laminar flow to the center ofthe sheath liquid laminar flow and thereby avoids the turbulence of thesample liquid laminar flow.

FIGS. 1A and 1B are schematic diagrams illustrating a channel structureformed on a microchip according to a first embodiment of the presentinvention, in which FIG. 1A shows a top view and FIG. 1B shows asectional view.

In the figures, the reference numeral 11 indicates a first introductionchannel (which is referred to hereinafter as a sample liquidintroduction channel 11) through which a first fluid (referred tohereinafter as a sample liquid) is introduced. The reference numerals 21and 22 indicate second introduction channels (referred to hereinafter assheath liquid introduction channels 21 and 22) which are arranged tosandwich the sample liquid introduction channel 11 and merged with thesample liquid introduction channel 11 from the both sides thereof, andthrough which a second fluid (referred to hereinafter as a sheathliquid) is introduced. Further, the reference numeral 12 indicates amerge channel which is connected to the sample liquid introductionchannel 11 and the sheath liquid introduction channels 21 and 22 andthrough which the sample liquid and the sheath liquids fed from therespective channels are merged and flow.

The sample liquid introduction channel 11 has, at the merging portionwith the sheath liquid introduction channels 21 and 22, a communicatingport 111 for introducing the sample liquid into the center of the mergechannel 12 through which the sheath liquid laminar flow T flows. Thechannel depth of the sample liquid introduction channel 11 in the Z-axisdirection is designed to be smaller than the channel depth of the sheathliquid introduction channels 21 and 22, and the communicating port 111is disposed at substantially the center position in the channel depthdirection of the sheath liquid introduction channels 21 and 22. Further,the communicating port 111 is also disposed at substantially the centerposition in the channel width direction (the Y-axis direction) of themerge channel 12.

By introducing the sample liquid laminar flow S to the center of thesheath liquid laminar flow T from the communicating port 111, the sampleliquid laminar flow S can be fed in the state of being surrounded by thesheath liquid laminar flow T (see also FIGS. 2A, 2B and 2C describednext). Note that the position where the communicating port 111 is placedis not limited to the center position of the channel depth direction ofthe sheath liquid introduction channels 21 and 22 and may be in itsvicinity, as long as it allows the sample liquid laminar flow S to befed into the merge channel 12 in the state of being surrounded by thesheath liquid laminar flow T. Likewise, the position of thecommunicating port 111 in the channel width direction of the mergechannel 12 is not limited to the center position and may be in itsvicinity.

In the figures, the reference numeral 122 indicates a tapered portionthat functions to suppress the spiral flow field generated after themerging of the sample liquid laminar flow and the sheath liquid laminarflows illustrated in FIG. 20. The tapered portion 122 is disposed in themerge channel 12 in close proximity to the merging portion of the sampleliquid introduction channel 11 with the sheath liquid introductionchannels 21 and 22. The tapered portion 122 is formed so that thechannel width in the sandwiching direction (the Y-axis direction) alongwhich the sample liquid introduction channel 11 is sandwiched by sheathliquid introduction channels 21 and 22 is enlarged gradually along thefeeding direction.

The fluid velocity vector field in the merge channel 12 and the functionof the tapered portion 122 are described with reference to FIGS. 1A and1B and FIGS. 2A to 2C. FIGS. 2A, 2B and 2C are schematic sectionaldiagrams of the merge channel 12, in which FIG. 2A shows section P-P,FIG. 2B shows section Q-Q, and FIG. 2C shows section R-R, respectivelyin FIGS. 1A and 1B.

When the sample liquid laminar flow S is introduced from an opening 111into the center of the sheath liquid laminar flow T flowing through themerge channel 12, a high velocity vector appears at the center in thedepth direction of the channel immediately after the introduction (seethe dotted-line arrows in FIG. 2A). The high velocity vector occursbecause the merged sample liquid laminar flow S and sheath liquidlaminar flows T are concentrated on the center of the depth direction ofthe channel for flowing faster as described earlier.

At the tapered portion 122, when the laminar flow width of the mergedsample liquid laminar flow S and sheath liquid laminar flow T isenlarged in the Y-axis direction, a flow field (see the solid-linearrows in FIG. 2B), which is in reverse direction to the high velocityvector generated at the center in the depth direction of the channel, isgenerated. By generating the reverse flow field, the tapered portion 122cancels out the flow field generated at the center in the depthdirection of the channel and thereby prevents the flow field fromgrowing into the spiral flow field. As a result, the sample liquidlaminar flow S is maintained in the state of being converted to thecenter of the channel without being stretched out in the Z-axisdirection by the spiral flow field (see FIGS. 2B and 2C).

In the figures, the reference numeral 121 indicates a contracted portionthat functions to narrow down the laminar flow width of the mergedsample liquid laminar flow S and sheath liquid laminar flow T in theY-axis direction and the Z-axis direction. The contracted portion 121 isdisposed on the downstream side of the tapered portion 122. Thecontracted portion 121 is formed so that the channel width is reducedgradually along the feeding direction. Further, the contracted portion121 is formed so that the channel depth is also reduced gradually alongthe feeding direction. Specifically, the channel wall of the contractedportion 121 is formed to be narrowed along the feeding direction in theY-axis and the Z-axis directions, and the contracted portion 121 isformed so that the area of the vertical section with respect to thefeeding direction (the X-axis positive direction) decreases gradually.With such a shape, the contracted portion 121 feeds the liquids bynarrowing down the laminar flow width of the merged sample liquidlaminar flow S and sheath liquid laminar flow T in the Y-axis directionand the Z-axis direction.

FIG. 3 and FIGS. 4A and 4B are schematic diagrams illustrating astructure of the communicating port 111. The channel depth of the sampleliquid introduction channel 11 in the Z-axis direction is designed to besmaller than the channel depth of the sheath liquid introductionchannels 21 and 22, and the communicating port 111 is placed atsubstantially the center position of the channel depth direction of thesheath liquid introduction channels 21 and 22 (see FIG. 3). Further, inorder to suppress the stagnant flow field generated in the vicinity, thecommunicating port 111 opens in an area including channel walls 211 and221 of the sheath liquid introduction channel 21 and the sheath liquidintroduction channel 22.

This is described specifically with reference to FIGS. 4A and 4B. First,a structure of the opening 104 in the channel structure according torelated art (see FIGS. 18A and 18B) is described with reference to FIG.4B. In the channel structure according to related art, by a shear forcewhich occurs between the sheath liquid laminar flows T and the sampleliquid laminar flow S due to the merging of the sheath liquids fed fromthe channels 102 and 102 and the sample liquid flowing out from theopening 104, an unstable flow field with a stagnant flow (the diagonallyshaded area in FIG. 4B) is generated in the vicinity of the opening 104(see also FIG. 21).

In this case, the sample liquid flows out to the stagnant, unstable flowfield from the opening 104. Consequently, the sample liquid laminar flowS becomes unstable before coming into contact with the fast-flowingsheath liquids fed from the channels 102 and 102 and dispersed in thedepth direction of the channel.

On the other hand, because the communicating port 111 of the microchipaccording to the embodiment opens in an area including the channel walls211 and 221 of the sheath liquid introduction channel 21 and the sheathliquid introduction channel 22, the sample liquid flowing out of thecommunicating port 111 comes into direct contact with the fast-flowingsheath liquids fed through the sheath liquid introduction channels 21and 22. Consequently, the sample liquid laminar flow S is accelerated bythe sheath liquids immediately after flowing out of the communicatingport 111 and thereby maintained in the stable state of being convertedto the center of the channel without being dispersed in the depthdirection.

Note that the shape of the communicating port 111 described herein maybe regarded as a shape that the side end of the communicating port 111of the sample liquid introduction channel 11 is cut out by the channelwalls 211 and 221 of the sheath liquid introduction channel 21 and thesheath liquid introduction channel 22. Because the shape of thecommunicating port 111 is made by the cutout by the channel walls 211and 221 of the sheath liquid introduction channel 21 and the sheathliquid introduction channel 22, the channel width indicated by thesymbol W in FIG. 4A is designed to be smaller than the channel widthafter cutout indicated by the symbol C.

3. Alternative Example of Channel Structure of Microchip According toFirst Embodiment

FIG. 1A illustrates the case where the tapered portion 122 is disposedin the merge channel 12 on the downstream side of the communicating port111, which is the merging portion of the sample liquid introductionchannel 11 with the sheath liquid introduction channels 21 and 22.However, the position where the tapered portion 122 is disposed is notlimited to the position shown in FIG. 1A, as long as it is in closeproximity to the merging portion of the sample liquid introductionchannel 11 with the sheath liquid introduction channels 21 and 22.

FIGS. 5A, 5B and 5C show alternative examples of the tapered portion122, in which the upper part shows a top schematic view and the lowerpart shows a sectional schematic view. As shown in FIG. 5A, for example,the tapered portion 122 may be placed so that the point at which thechannel width in the Y-axis direction begins to increase is located onthe upstream side of the communicating port 111. Further, as shown inFIG. 5B, the tapered portion 122 may be placed so that the point atwhich the channel width in the Y-axis direction begins to increase islocated at the position coinciding with the communicating port 111. Notethat FIG. 5C shows the case where the point at which the channel widthin the Y-axis direction begins to increase is located on the downstreamside of the communicating port 111 and the tapered portion 122 is placedon the downstream side of the communicating port 111.

4. Microchip According to Second Embodiment of Invention

FIGS. 6A and 6B are schematic diagrams illustrating a channel structureon a microchip according to a second embodiment of the presentinvention, in which FIG. 6A shows a top view and FIG. 6B shows asectional view.

In the figures, the reference numeral 11 indicates a sample liquidintroduction channel through which a sample liquid is introduced. Thereference numerals 21 and 22 indicate sheath liquid introductionchannels which are arranged to sandwich the sample liquid introductionchannel 11 and merged with the sample liquid introduction channel 11from the both sides thereof, and through a sheath liquid is introduced.Further, the reference numeral 12 indicates a merge channel which isconnected to the sample liquid introduction channel 11 and the sheathliquid introduction channels 21 and 22 and through which the sampleliquid and the sheath liquids fed from the respective channels aremerged and flow.

The sample liquid introduction channel 11 has, at the merging portionwith the sheath liquid introduction channels 21 and 22, a communicatingport 111 for introducing the sample liquid into the center of the mergechannel 12 through which the sheath liquid laminar flow T flows.

The channel depth of the sample liquid introduction channel 11 in theZ-axis direction is designed to be smaller than the channel depth of thesheath liquid introduction channels 21 and 22, and the communicatingport 111 is disposed at substantially the center position in the channeldepth direction of the sheath liquid introduction channels 21 and 22.Further, the communicating port 111 is also disposed at substantiallythe center position in the channel width direction (the Y-axisdirection) of the merge channel 12.

By introducing the sample liquid laminar flow S to the center of thesheath liquid laminar flow T from the communicating port 111, the sampleliquid laminar flow S can be fed in the state of being surrounded by thesheath liquid laminar flow T (see also FIG. 7 described next). Note thatthe position where the communicating port 111 is placed is not limitedto the center position of the channel depth direction of the sheathliquid introduction channels 21 and 22 and may be in its vicinity, aslong as it allows the sample liquid laminar flow S to be fed into themerge channel 12 in the state of being surrounded by the sheath liquidlaminar flow T. Likewise, the position of the communicating port 111 inthe channel width direction of the merge channel 12 is not limited tothe center position and may be in its vicinity.

In the figures, the reference numeral 123 indicates a tapered portionthat functions to suppress the spiral flow field generated after themerging of the sample liquid laminar flow and the sheath liquid laminarflows illustrated in FIG. 20. The tapered portion 123 is disposed in themerge channel 12 in close proximity to the merging portion of the sampleliquid introduction channel 11 with the sheath liquid introductionchannels 21 and 22. The tapered portion 123 is formed so that thechannel depth in the vertical direction (the Z-axis direction)perpendicular to the plane (X-Y plane) containing the sample liquidintroduction channel 11 and the sheath liquid introduction channels 21and 22 is narrowed gradually along the feeding direction.

The fluid velocity vector field in the merge channel 12 and the functionof the tapered portion 123 are described with reference to FIGS. 6A and6B and FIGS. 7A to 7C. FIGS. 7A, 7B and 7C are schematic sectionaldiagrams of the merge channel 12, in which FIG. 7A shows section P-P,FIG. 7B shows section Q-Q, and FIG. 7C shows section R-R, respectivelyin FIGS. 6A and 6B.

When the sample liquid laminar flow S is introduced from an opening 111into the center of the sheath liquid laminar flow T flowing through themerge channel 12, a high velocity vector appears at the center in thedepth direction of the channel immediately after the introduction (seethe dotted-line arrows in FIG. 7A). The high velocity vector occursbecause the merged sample liquid laminar flow S and sheath liquidlaminar flows T are concentrated on the center of the depth direction ofthe channel for flowing faster as described earlier.

At the tapered portion 123, when the laminar flow width of the mergedsample liquid laminar flow S and sheath liquid laminar flow T isnarrowed in the Z-axis direction, a flow field (see the solid-linearrows in FIG. 7B), which is in reverse direction to the high velocityvector generated at the center in the depth direction of the channel, isgenerated. By generating the reverse flow field, the tapered portion 123cancels out the flow field generated at the center in the depthdirection of the channel and thereby prevents the flow field fromgrowing into the spiral flow field. As a result, the sample liquidlaminar flow S is maintained in the state of being converted to thecenter of the channel without being stretched out in the Z-axisdirection by the spiral flow field (see FIGS. 7B and 7C).

In the figures, the reference numeral 121 indicates a contracted portionthat functions to narrow down the laminar flow width of the mergedsample liquid laminar flow S and sheath liquid laminar flow T in theY-axis direction and the Z-axis direction. The structure and the actionof the contracted portion 121 are the same as those in the microchipaccording to the first embodiment and not redundantly described.Further, the structure and the action of the communicating port 111 arealso the same as those in the microchip according to the firstembodiment.

5. Alternative Example of Channel Structure of Microchip According toSecond Embodiment

FIG. 6B illustrates the case where the tapered portion 123 is disposedso that the point at which the channel depth in the Z-axis directionbegins to decrease coincides with the position of the communicating port111. However, the position where the tapered portion 123 is disposed isnot limited to the position shown in FIG. 6B, as long as it is in closeproximity to the merging portion of the sample liquid introductionchannel 11 with the sheath liquid introduction channels 21 and 22.

FIGS. 8A, 8B and 8C show alternative examples of the tapered portion123, in which the upper part shows a top schematic view and the lowerpart shows a sectional schematic view, of the tapered portion 123. Asshown in FIG. 8A, for example, the tapered portion 123 may be placed sothat the point at which the channel depth in the Z-axis direction beginsto decrease is located on the upstream side of the communicating port111. Further, as shown in FIG. 8C, the tapered portion 123 may be placedso that the point at which the channel depth in the Z-axis directionbegins to decrease is located on the downstream side of thecommunicating port 111. Note that FIG. 8B shows the case where the pointat which the channel depth in the Z-axis direction begins to decrease islocated at the position coinciding with the communicating port 111 as inthe case of FIGS. 6A and 6B.

A taper angle (see the symbol (theta)z in FIGS. 9A and 9B) in thechannel depth direction of the tapered portion 123 may be set to anyvalue as long as the function of the tapered portion 123 can be exerted.By setting the taper angle (theta)z to be larger than the merging angle(see the symbol (theta)y in FIG. 9A) of the sheath liquid introductionchannels 21 and 22 with the sample liquid introduction channel 11, theeffect of suppressing the generation of the spiral flow field can beenhanced. Further, in the case where the channel width of the mergechannel 12 is designed to be reduced gradually along the feedingdirection, by setting the taper angle (theta)z to be larger than thedraw angle (see the symbol (theta)y in FIG. 9B) of the merge channel 12,the sufficient effect of suppressing the spiral flow field can beobtained.

Although the case where the tapered portion 123 and the contractedportion 121 are formed discontinuously is illustrated in FIGS. 6A and6B, the tapered portion 123 and the contracted portion 121 may be formedcontinuously as illustrated in FIGS. 10A and 10B.

6. Microchip According to Third Embodiment of Invention

FIGS. 11A and 11B are schematic diagrams illustrating a channelstructure on a microchip according to a third embodiment of the presentinvention, in which FIG. 11A shows a top view and FIG. 11B shows asectional view, respectively of the microchip.

In the figures, the reference numeral 11 indicates a sample liquidintroduction channel through which a sample liquid is introduced. Thereference numerals 21 and 22 indicate sheath liquid introductionchannels which are arranged to sandwich the sample liquid introductionchannel 11 and merged with the sample liquid introduction channel 11from the both sides thereof, and through a sheath liquid is introduced.Further, the reference numeral 12 indicates a merge channel which isconnected to the sample liquid introduction channel 11 and the sheathliquid introduction channels 21 and 22 and through which the sampleliquid and the sheath liquids fed from the respective channels aremerged and flow.

The sample liquid introduction channel 11 has, at the merging portionwith the sheath liquid introduction channels 21 and 22, a communicatingport 111 for introducing the sample liquid into the center of the mergechannel 12 through which the sheath liquid laminar flow T flows.

The channel depth of the sample liquid introduction channel 11 in theZ-axis direction is designed to be smaller than the channel depth of thesheath liquid introduction channels 21 and 22, and the communicatingport 111 is disposed at substantially the center position in the channeldepth direction of the sheath liquid introduction channels 21 and 22.Further, the communicating port 111 is also disposed at substantiallythe center position in the channel width direction (the Y-axisdirection) of the merge channel 12.

By introducing the sample liquid laminar flow S to the center of thesheath liquid laminar flow T from the communicating port 111, the sampleliquid laminar flow S can be fed in the state of being surrounded by thesheath liquid laminar flow T (see also FIG. 12 described next). Notethat the position where the communicating port 111 is placed is notlimited to the center position of the channel depth direction of thesheath liquid introduction channels 21 and 22 and may be in itsvicinity, as long as it allows the sample liquid laminar flow S to befed into the merge channel 12 in the state of being surrounded by thesheath liquid laminar flow T. Likewise, the position of thecommunicating port 111 in the channel width direction of the mergechannel 12 is not limited to the center position and may be in itsvicinity.

In the figures, the reference numerals 122 and 123 indicate taperedportions that function to suppress the spiral flow field generated afterthe merging of the sample liquid laminar flow and the sheath liquidlaminar flows illustrated in FIG. 20. The tapered portions 122 and 123are disposed in the merge channel 12 in close proximity to the mergingportion of the sample liquid introduction channel 11 with the sheathliquid introduction channels 21 and 22. The tapered portion 122 isformed so that the channel width in the sandwiching direction (theY-axis direction) along which the sample liquid introduction channel 11is sandwiched by sheath liquid introduction channels 21 and 22 isenlarged gradually along the feeding direction. Further, the taperedportion 123 is formed so that the channel depth in the verticaldirection (the Z-axis direction) perpendicular to the plane (X-Y plane)containing the sample liquid introduction channel 11 and the sheathliquid introduction channels 21 and 22 is narrowed gradually along thefeeding direction. In the microchip according to the embodiment, thetapered portions 122 and 123 are formed in a partially overlap area ofthe merge channel 12.

The fluid velocity vector field in the merge channel 12 and the functionof the tapered portions 122 and 123 are described with reference toFIGS. 11A and 11B and FIGS. 12A to 12C. FIGS. 12A, 12B and 12C areschematic sectional diagrams of the merge channel 12, in which FIG. 12Ashows section P-P, FIG. 12B shows section Q-Q, and FIG. 12C showssection R-R, respectively in FIGS. 11A and 11B.

When the sample liquid laminar flow S is introduced from an opening 111into the center of the sheath liquid laminar flow T flowing through themerge channel 12, a high velocity vector appears at the center in thedepth direction of the channel immediately after the introduction (seethe dotted-line arrows in FIG. 12A). The high velocity vector occursbecause the merged sample liquid laminar flow S and sheath liquidlaminar flows T are concentrated on the center of the depth direction ofthe channel for flowing faster as described earlier.

At the tapered portion 122, when the laminar flow width of the mergedsample liquid laminar flow S and sheath liquid laminar flow T isenlarged in the Y-axis direction, and at the tapered portion 123, whenthe laminar flow width of the merged sample liquid laminar flow S andsheath liquid laminar flow T is narrowed in the Z-axis direction, a flowfield (see the solid-line arrows in FIG. 12B), which is in reversedirection to the high velocity vector generated at the center in thedepth direction of the channel, is generated. By generating the reverseflow field, the tapered portions 122 and 123 cancel out the flow fieldgenerated at the center in the depth direction of the channel andthereby prevent the flow field from growing into the spiral flow field.As a result, the sample liquid laminar flow S is maintained in the stateof being converted to the center of the channel without being stretchedout in the Z-axis direction by the spiral flow field (see FIGS. 12B and12C).

In the figures, the reference numeral 121 indicates a contracted portionthat functions to narrow down the laminar flow width of the mergedsample liquid laminar flow S and sheath liquid laminar flow T in theY-axis direction and the Z-axis direction. The structure and the actionof the contracted portion 121 are the same as those in the microchipaccording to the first embodiment and not redundantly described.Further, the structure and the action of the communicating port 111 arealso the same as those in the microchip according to the firstembodiment.

7. Alternative Example of Channel Structure of Microchip According toThird Embodiment

FIG. 11A illustrates the case where the tapered portion 122 is disposedin the merge channel 12 on the downstream side of the communicating port111, which is the merging portion of the sample liquid introductionchannel 11 with the sheath liquid introduction channels 21 and 22.However, the position where the tapered portion 122 is disposed is notlimited to the position shown in FIG. 11A, as long as it is in closeproximity to the merging portion of the sample liquid introductionchannel 11 with the sheath liquid introduction channels 21 and 22.

Further, FIG. 11B illustrates the case where the tapered portion 123 isdisposed so that the point at which the channel depth in the Z-axisdirection begins to decrease coincides with the position of thecommunicating port 111. However, the position where the tapered portion123 is disposed is not limited to the position shown in FIG. 11B, aslong as it is in close proximity to the merging portion of the sampleliquid introduction channel 11 with the sheath liquid introductionchannels 21 and 22.

Furthermore, FIGS. 11A and 11B illustrate the case where the point ofthe tapered portion 123 at which the channel depth in the Z-axisdirection begins to decrease is disposed on the upstream side of thepoint of the tapered portion 122 at which the channel width in theY-axis direction begins to increase. However, the point at which thetapered portion 122 begins and the point at which the tapered portion123 begins may be different or the same. Likewise, although FIGS. 11Aand 11B illustrate the case where the point of the tapered portion 122at which the channel width in the Y-axis direction ends to increase andthe point of the tapered portion 123 at which the channel depth in theZ-axis direction ends to decrease are disposed on the same position, thepoint at which the tapered portion 122 ends and the point at which thetapered portion 123 ends may be different or the same.

FIG. 13 shows an alternative example of the tapered portions 122 and123. In this alternative example, the positions of the point of thetapered portion 122 at which the channel width in the Y-axis directionbegins to increase and the point of the tapered portion 123 at which thechannel depth in the Z-axis direction begins to decrease both coincidewith the communicating port 111. Further, the positions of the point atwhich the tapered portion 122 ends and the point at which the taperedportion 123 ends also coincide with each other.

Further, although the case where the tapered portion 123 and thecontracted portion 121 are formed discontinuously is illustrated inFIGS. 11A and 11B, the tapered portion 123 and the contracted portion121 may be formed continuously as illustrated in FIGS. 14A and 14B.

8. Manufacturing of Microchip According to Invention

The material of the microchip according to the embodiment of the presentinvention may be glass or various kinds of plastic (PP, PC, COP, PDMS).In the case where the analysis using the microchip is carried outoptically, it is preferred to select a material having lighttransmittance, with low autofluorescence, and with small optical errorsbecause of small wavelength dispersion.

In order to maintain the light transmittance of the microchip, itssurface is preferably coated with a so-called hard coat layer which isused for an optical disc. If a stain such as fingerprints is attached tothe surface of the microchip, particularly, the surface of an opticaldetector, the amount of light transmission decreases to cause thedegradation of accuracy of optical analyses. By depositing the hard coatlayer with high transparency and stain resistance on the surface of themicrochip, the degradation of accuracy of analysis can be prevented.

The hard coat layer can be formed by use of one of the hard coatingagents which are used ordinarily, for example, a UV-curing type hardcoating agent admixed with a fingerprint stain-proofing agent such as afluoro or silicone stain-proofing agent. Japanese Patent Laid-open No.2003-157579 discloses an active energy ray curable composition (P) as ahard-code agent which contains a multifunctional compound (A) having atleast two polymerizable functional groups capable of being polymerizedunder active energy rays, modified colloidal silica (B) whose averageparticle diameter is 1 to 200 nm, and whose surface has been modified bya mercaptosilane compound in which an organic group having a mercaptogroup and a hydrolysable group or hydroxyl group are bonded to siliconatom, and a photopolymerization initiator (C).

Forming of the sample liquid introduction channel 11, the sheath liquidintroduction channels 21 and 22, the merge channel 12 having the taperedportions 122 and 123 and the contracted portion 121 and the likearranged in the microchip can be carried out by wet etching or dryetching of a glass-made substrate layer, or by nanoimprint technique orinjection molding or cutting of a plastic-made substrate layer. Then,the two substrates on which the sample liquid introduction channel 11and the like is formed are laminated onto each other, whereby themicrochip can be fabricated. The lamination of the substrates onto eachother can be carried out by appropriately using a known method, such asheat fusing, adhesion with an adhesive, anodic bonding, bonding by useof a pressure sensitive adhesive-coated sheet, plasma-activated bonding,ultrasonic bonding, etc.

A manufacturing method of the microchip according to the embodiment ofthe present invention is described hereinafter with reference to FIGS.15A and 15B and FIGS. 16A and 16B. FIGS. 15A and 15B show top schematicdiagrams of substrates constituting the microchip according to theembodiment of the present invention. FIGS. 16A and 16B show sectionaldiagrams of the microchip according to the embodiment of the presentinvention. FIG. 16B shows section P-P in FIG. 16A.

First, part of the sheath liquid introduction channels 21 and 22 andpart of the merge channel 12 are made on a substrate a (see FIG. 15A).On the substrate a, a sample liquid supply port 3 for supplying a sampleliquid to the sample liquid introduction channel 11, a sheath liquidsupply port 4 for supplying a sheath liquid to the sheath liquidintroduction channels 21 and 22, and an discharge port for dischargingthe sample liquid and the sheath liquid from the merge channel 12 arealso made. Next, the sample liquid introduction channel 11, part of thesheath liquid introduction channels 21 and 22 and part of the mergechannel 12 are made on a substrate b (see FIG. 15B).

Next, the substrate a and the substrate b are laminated onto each otherby thermocompression bonding or the like as shown in FIGS. 16A and 16B,whereby the microchip can be fabricated. In this step, the sheath liquidintroduction channels 21 and 22 are created at different depths on thesubstrates a and b so that the sample liquid introduction channel 11 islocated at substantially the center in the channel depth direction ofthe sheath liquid introduction channels 21 and 22.

As described above, the microchip according to the embodiment of thepresent invention may be manufactured by laminating the substrates a andb on which the sample liquid introduction channel 11 and the like ismade. Therefore, differently from the microchip disclosed in theabove-described Patent Literature 2 in which the guide structure isprovided at the opening of the channel for introducing the sample liquidlaminar flow, the microchip according to the embodiment of the presentinvention can be manufactured by the lamination of two substrates only.The formation of the channel structure onto each substrate and thelamination of the substrates are thus easy, thereby suppressing themanufacturing cost of the microchip.

9. Particulate Analyzing Device According to Invention

The above-described microchip can be incorporated into a particulateanalyzing device according to an embodiment of the present invention.The particulate analyzing device is applicable as a particulatefractionating device that analyzes the characteristics of particulatesand performs fractionation of particulates on the basis of theanalytical results.

In the particulate analyzing device, a detector (see the symbol D inFIG. 15B) for detecting particulates contained in the sample liquid fedfrom the sample liquid introduction channel 11 is placed on thedownstream side of the tapered portion 122 or 123 and the contractedportion 121 in the merge channel 12 of the microchip.

The microchip according to the embodiment of the present invention makesit possible, with the tapered portion 122, 123, to feed the sampleliquid laminar flow S in the state of being converted to the center ofthe merge channel 12 and thereby eliminate the dispersion of the feedingposition of the particulates in the depth direction of the channel andthe difference in the flowing speed of the particulates caused by thedispersion (see FIG. 2 etc.). Thus, by placing the detecting portion Don the downstream side of the tapered portion 122, 123 and detectingparticulates, it is possible to eliminate the variation of detectionsignals caused by the difference in the flowing speed of theparticulates and thereby achieve the detection of particulates with highaccuracy.

Further, the microchip according to the embodiment of the presentinvention makes it possible, with the contracted portion 121, to feedthe liquids by narrowing down the laminar flow width of the sampleliquid laminar flow S and the sheath liquid laminar flow T in thechannel width direction and depth direction. By narrowing down thelaminar flow width of the sample liquid laminar flow S and the sheathliquid laminar flow T, the particulates can be made to be arranged in arow in the sample liquid laminar flow S, and the dispersion of thefeeding position of the particulates in the depth direction of thechannel and the difference in the flowing speed of the particulatescaused by the dispersion can be further reduced. Thus, by placing thedetecting portion D on the downstream side of the contracted portion 121and detecting particulates, it is possible to detect the particulatesone by one and also make detection by eliminating the variation ofdetection signals caused by the difference in the flowing speed of theparticulates as much as possible.

The detecting portion D may be configured as an optical detectionsystem, an electrical detection system, or a magnetic detection system.Those detection systems may be configured in the same manner as those inparticulate analyzing systems using microchips according to related art.Specifically, the optical detection system includes a laser beam source,an irradiation section composed of a condenser lens and the like forcondensing the laser beam and irradiating each of the particulates withthe laser beam, and a detection system for detecting the light generatedfrom the particulate upon irradiation with the laser beam by use of adichroic mirror, a bandpass filter and the like. The detection of thelight generated from particulates may be made by an area image pick-upelement such as a PMT (photo multiplier tube), a CCD or a CMOS device,for example. Further, the electrical detection system or the magneticdetection system places micro-electrodes on the channel of the detectingportion D and thereby measure, for example, resistance, capacitance,inductance, impedance, variation in electric field between theelectrodes or the like, or, alternatively, magnetization, variation inmagnetic field or the like.

The light, resistance, magnetization or the like generated from theparticulates detected in the detecting portion D is converted into anelectrical signal and output to a total control unit. Note that thelight to be detected may be forward scattered light or side-wayscattered light from the particulate, or scattered light, fluorescentlight or the like arising from Reyleigh scattering, Mie scattering orthe like.

Based on the electrical signal inputted, the total control unit measuresthe optical characteristics of the particulates. A parameter for themeasurement of the optical characteristics is selected according to theparticulates under consideration and the purpose of fractionalcollection. Specifically, forward scattered light is adopted in the caseof determining the size of the particulates, side-way scattered light isadopted in the case of determination of structure, and fluorescent lightis adopted in the case of determining whether a fluorescent materiallabeling the particulate is present or absent.

Further, the particulate analyzing device according to the embodiment ofthe present invention may be provided with the particulate fractionatingchannel as disclosed in the above Patent Literature 1 and an electrodefor controlling the moving direction of particulates disposed near achannel port to the particulate fractionating channel, so as to analyzethe characteristics of the particulates by the total control unit andperform fractionation of the particulates based on the analyticalresults.

The microchip according to the embodiment of the present invention iseasily manufacturable and capable of feeding the sample liquid laminarflow being converged to the center of the channel. Therefore, whenanalyzing the characteristics of particulates by feeding a solutioncontaining the particulates as a sample liquid through the channel, highanalysis accuracy can be obtained by eliminating the dispersion of thefeeding position of the particulates in the depth direction of thechannel. Therefore, the microchip according to the embodiment of thepresent invention is suitably applicable to the particulate analyzingtechnology which analyzes the characteristics of particulates such ascells and microbeads optically, electrically or magnetically.

It should be understood that various changes and modifications to thepresently preferred embodiments described herein will be apparent tothose skilled in the art. Such changes and modifications can be madewithout departing from the spirit and scope of the present invention andwithout diminishing its intended advantages. It is therefore intendedthat such changes and modifications be covered by the appended claims.

1. A microfluidic chip for use with a particulate analyzing device, themicrofluidic chip comprising: a substrate; and a fluid channel formed inthe substrate, the fluid channel including: a supply port configured toreceive a sample liquid flow; and a merge channel configured to convertthe sample liquid flow into a sheath liquid laminar flow, the mergechannel having a first fluid converting structure, a second fluidconverting structure, and a third fluid converting structure, to convertthe sample liquid flow into the sheath liquid laminar flow byintroducing sheath liquid into the fluid channel or changing a crosssection area, wherein the first, second, and third fluid convertingstructures are provided at different longitudinal locations along thefluid channel, a first surface portion of the fluid channel lies in afirst plane upstream of the second and third fluid convertingstructures, a second surface portion of the fluid channel lies in asecond plane vertically above the first plane downstream of the secondand third fluid converting structures, and the first fluid convertingstructure having a tapered portion narrowing the sample liquid flow in afirst direction, the second fluid converting structure having a firstportion narrowing the sample liquid flow in a second direction, and thethird fluid converting structure having a second portion narrowing thesample liquid flow in the second direction, and the first direction isorthogonal to the second direction.
 2. The microfluidic chip of claim 1,further comprising a detection portion downstream of the first, second,and third fluid converting structures.
 3. The microfluidic chip of claim1, wherein the first fluid converting structure is configured tointroduce sheath liquid into the fluid channel symmetrically withrespect to a centerline of the sample liquid flow.
 4. The microfluidicchip of claim 1, wherein the first fluid converting structure isconfigured to convert the sample liquid flow in at least a lateraldirection.
 5. The microfluidic chip of claim 1, wherein the second fluidconverting structure is configured to convert the sample liquid flow inat least a vertical direction.
 6. The microfluidic chip of claim 1,wherein the third fluid converting structure is configured to convertthe sample liquid flow in at least a vertical direction.
 7. Themicrofluidic chip of claim 1, wherein the sample liquid flow and thesheath liquid associated with the first fluid converting structure enterthe merge channel in a center line.
 8. The microfluidic chip of claim 1,wherein the merge channel has a varying width upstream of the second andthird fluid converting structures; and wherein the fluid channel has aconstant width between the second fluid converting structure and thirdfluid converting structure.
 9. The microfluidic chip of claim 8, whereinthe fluid channel has a constant width between a detection portion andthe second and third fluid converting structures.
 10. The microfluidicchip of claim 1, wherein within the merge channel the fluid channeltransitions from a first cross section shape to a second cross sectionshape different from the first cross section shape.
 11. The microfluidicchip of claim 1, wherein a first surface of the fluid channel lies in athird plane upstream of the first and second fluid convertingstructures, and a second surface of the fluid channel lies in a fourthplane vertically below the third plane downstream of the first andsecond fluid converting structures.
 12. The microfluidic chip of claim1, wherein the first portion includes a tapered portion.
 13. Themicrofluidic chip of claim 1, wherein the second portion includes acontracted portion.
 14. The microfluidic chip of claim 1, wherein themerge channel includes a focusing region.
 15. A particulate analyzingdevice comprising: a detector configured to detect particulates in asample liquid flow in a fluid channel formed in a substrate on amicrofluidic chip, the fluid channel including: a supply port configuredto receive the sample liquid flow; and a merge channel configured toconvert the sample liquid flow into a sheath liquid laminar flow, themerge channel having a first fluid converting structure, a second fluidconverting structure, and a third fluid converting structure, to convertthe sample liquid flow into the sheath liquid laminar flow byintroducing sheath liquid into the fluid channel or changing a crosssection area, wherein the first, second, and third fluid convertingstructures are provided at different longitudinal locations along thefluid channel, a first surface portion of the fluid channel lies in afirst plane upstream of the second and third fluid convertingstructures, a second surface portion of the fluid channel lies in asecond plane vertically above the first plane downstream of the secondand third fluid converting structures, and the first fluid convertingstructure is a tapered portion narrowing the sample liquid flow in afirst direction, the second fluid converting structure is a firstportion narrowing the sample liquid flow in a second direction, and thethird fluid converting structure is a second portion narrowing thesample liquid flow in the second direction, and the first direction isorthogonal to the second direction.
 16. The particulate analyzing deviceof claim 15, further comprising: a detection portion in the microfluidicchip downstream of the first, second, and third fluid convertingstructures.
 17. The particulate analyzing device of claim 15, whereinthe first fluid converting structure is configured to introduce sheathliquid into the fluid channel symmetrically with respect to a centerlineof the sample liquid flow.
 18. The particulate analyzing device of claim15, wherein the first fluid converting structure is configured toconvert the sample liquid flow in at least a lateral direction.
 19. Theparticulate analyzing device of claim 15, wherein the second fluidconverting structure is configured to convert the sample liquid flow inat least a vertical direction.
 20. The particulate analyzing device ofclaim 15, wherein the third fluid converting structure is configured toconvert the sample liquid flow in at least a vertical direction.
 21. Theparticulate analyzing device of claim 15, wherein the sample liquid flowand the sheath liquid associated with the first fluid convertingstructure enter the merge channel in a center line.
 22. The particulateanalyzing device of claim 15, wherein the merge channel has a varyingwidth upstream of the second and third fluid converting structures; andwherein the fluid channel has a constant width between the second fluidconverting structure and third fluid converting structure.
 23. Theparticulate analyzing device of claim 22, wherein the fluid channel hasa constant width between a detection portion and the second and thirdfluid converting structures.
 24. The particulate analyzing device ofclaim 15, wherein within the merge channel the fluid channel transitionsfrom a first cross section shape to a second cross section shapedifferent from the first cross section shape.
 25. The particulateanalyzing device of claim 15, wherein a first surface of the fluidchannel lies in a third plane upstream of the first and second fluidconverting structures, and a second surface of the fluid channel lies ina fourth plane vertically below the third plane downstream of the firstand second fluid converting structures.
 26. The particulate analyzingdevice of claim 15, wherein the sample liquid flow is narrowed such thatthe particulates are arranged in a row downstream of the second andthird fluid converting structures, and the detector is configured todetect the particulates one by one.
 27. The particulate analyzing deviceof claim 15, wherein the detector is included in at least one of anoptical detection system, an electrical detection system, or a magneticdetection system.
 28. The particulate analyzing device of claim 15,further comprising an optical detection system, which includes thedetector, a laser beam source, an irradiation section including acondenser lens configured to condense the laser beam and irradiate theparticulates, a dichroic mirror, and a bandpass filter.
 29. Theparticulate analyzing device of claim 15, wherein the detector comprisesa pick-up element which is at least one of a photo multiplier tube, aCCD or a CMOS device.
 30. A system comprising: a particulate analyzingdevice; and a microfluidic chip, wherein the microfluidic chipcomprises: a substrate; and a fluid channel formed in the substrate, thefluid channel including: a supply port configured to receive a sampleliquid flow; and a merge channel configured to convert the sample liquidflow into a sheath liquid laminar flow, the merge channel having a firstfluid converting structure, a second fluid converting structure, and athird fluid converting structure, to convert the sample liquid flow intothe sheath liquid laminar flow by introducing sheath liquid into thefluid channel or changing a cross section area, wherein the first,second, and third fluid converting structures are provided at differentlongitudinal locations along the fluid channel, a first surface portionof the fluid channel lies in a first plane upstream of the second andthird fluid converting structures, a second surface portion of the fluidchannel lies in a second plane vertically above the first planedownstream of the second and third fluid converting structures, and thefirst fluid converting structure having a tapered portion narrowing thesample liquid flow in a first direction, the second fluid convertingstructure having a first portion narrowing the sample liquid flow in asecond direction, and the third fluid converting structure having asecond portion narrowing the sample liquid flow in the second direction,and the first direction is orthogonal to the second direction.